A basic understanding of the retinal function requires establishing the identities and characteristics of neurotransmitters involved in retinal information processing. Studies in this laboratory and by others have indicated the presence of a serotonin (5-HT) system in the retina. This proposal is designed to establish the neurochemical and pharmacological characteristics of serotonin system in the retina of three species of animals (bovine, rabbit, and rat). The overall goal of the project is to, a) establish the cellular localization and biochemical characteristics of the 5-HT system, b) determine the response of the system to physiological stimuli and pharmacological manipulations, and c) identify the interaction of 5-HT with other retinal neurotramitters and establish the role of 5-HT in vision through behavioral studies. Biochemical techniques to be used include fractionation, estimation of indoleamine concentration, activity of enzymes (tryptophan hydroxylase, monoamine oxidase and adenylate cyclase), uptake and evoked release, and receptor binding. Pharmacology of retinal 5-HT system will be tested by the in vitro and in vivo use of an extensive array of drugs such as hallucinogens, antipsychotics, and antidepressants. Morphological studies will consist of light and electronmicroscopic examination, and autoradiography. Behavioral effects will be assessed following selective lesioning of retinal 5-HT and dopamine neurons. The success of similar studies in the brain and the results of initial retina experiments in this laboratory demonstrate the effectiveness of the approach advocated in this proposal. This study will significantly contribute to our understanding of retinal neurotramitter physiology, clarify the pharmacological actions of some of the widely abused as well as some clinically used drus, and provide new insight into the cellular mechanisms that regulate 5-HT system in the retina. In addition, this information will be useful in formulating a model for other more complex and less accessible neuronal systems such as the brain, in terms of how neurotransmitter systems interact to produce their final output.